Discovery of New Carbonyl Reductases Using Functional Metagenomics and Applications in Biocatalysis.
Enzyme discovery for use in the manufacture of chemicals, requiring high stereoselectivities, continues to be an important avenue of research. Here, a sequence directed metagenomics approach is described to identify short chain carbonyl reductases. PCR from a metagenomic template generated 37 enzymes, with an average 25% sequence identity, twelve of which showed interesting activities in initial screens. Six of the most productive enzymes were then tested against a panel of 21 substrates, including bulkier substrates that have been noted as challenging in biocatalytic reductions. Two enzymes were selected for further studies with the Wieland Miescher ketone. Notably, enzyme SDR-17, when co-expressed with a co-factor recycling system produced the anti-(4aR,5S) isomer in excellent isolated yields of 89% and 99% e.e. These results demonstrate the viability of a sequence directed metagenomics approach for the identification of multiple homologous sequences with low similarity, that can yield highly stereoselective enzymes with applicability in industrial biocatalysis.


Ethnic Differences in the Association Between Age-Related Macular Degeneration and Vision-Specific Functioning.
Understanding the link between ethnicity and health is critical to making appropriate public policy decisions. Few population-level data are available about this connection, however, including the influence of ethnicity on the association between age-related macular degeneration (AMD) and vision-specific functioning (VSF). To identify the influence of ethnicity on VSF among Chinese, Malay, and Indian patients with AMD. This cross-sectional, population-based study relied on patients and their data from 3 population-based studies in 3 ethnic groups: Chinese, Malay and Indian. Of 10 033 Chinese, Malay, and Indian adults who participated in the study, 9962 (99.3%) who had gradable fundus images and Visual Function Index (VF-11) data available were included in the analyses for the present study. Uniocular presenting distance visual acuity was measured using the logMAR chart. Separate multiple linear regression models examined the association between AMD and VSF in the 3 ethnic groups, adjusting for age, sex, presenting visual acuity in the better-seeing eye, educational level, income, smoking status, hypertension, diabetes, cardiovascular disease, total cholesterol level, and other eye conditions. Data were collected between January 20, 2004, and December 19, 2011; data analysis was conducted between November 12, 2015, and December 28, 2016. Age-related macular degeneration according to fundus photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System. Rasch analysis was used to convert VF-11 questionnaire scores to estimated interval measures of VSF. Of the 9962 participants, the mean (SD) age was 58.8 (10.4) years; 4909 (49.3%) were male; 590 (5.9%) had early AMD (241 Chinese, 161 Malays, and 188 Indians) and 60 (0.6%) had late AMD (25 Chinese, 21 Malays, and 14 Indians). In the adjusted models, compared with no AMD, early AMD was associated with a small reduction in VSF (2.9%; β = -0.12; 95% CI, -0.23 to -0.00; P = .046) in the Chinese group but not in the Indian and Malay groups. Moreover, Chinese participants with late AMD had a clinically significant 19.1% loss of VSF (β = -0.78; 95% CI, -1.13 to -0.43, P < .001). In the Malay group, those with late AMD had a 13.5% drop in VSF (β = -0.49; 95% CI, -1.01 to 0.04; P = .07) compared with their counterparts without AMD. Similarly, late AMD was not associated with VSF in the Indian group. Early and late AMD negatively affected VSF in Chinese but not in Indian and Malay participants. This finding suggests that there is an independent ethnic influence in the association of the disease with VSF in multiethnic Asian populations, thus warranting ethnicity-based strategies to delay the onset or progression of AMD.


A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy.
Systemic delivery of an anti-cancer agent often leads to only a small fraction of the administered dose accumulating in target sites. Delivering anti-cancer agents through the lymphatic network can achieve more efficient drug delivery for the treatment of lymph node metastasis. We show for the first time that polymeric gold nanorods (PAuNRs) can be delivered efficiently from an accessory axillary lymph node to a tumor-containing proper axillary lymph node, enabling effective treatment of lymph node metastasis. In a mouse model of metastasis, lymphatic spread of tumor was inhibited by lymphatic-delivered PAuNRs and near-infrared laser irradiation, with the skin temperature controlled by cooling. Unlike intravenous injection, lymphatic injection delivered PAuNRs at a high concentration within a short period. The results show that lymphatic administration has the potential to deliver anti-cancer agents to metastatic lymph nodes for inhibition of tumor growth and could be developed into a new therapeutic method.


Malignant Giant Cell Tumor of Soft Tissue: A Case Report of Intramuscular Malignant Giant Cell Carcinoma of the Tensor Fasciae Latae.
Giant cell tumor of soft tissue (GCT-ST)is a low-grade ST tumor that occurs most frequently below the skin and sometimes, extending deeper into the tissues. The tumor is usually hard, painless and considered rare in ST. We report a rare case of a middle-aged woman that presented with a tumor arising from the right tensor fasciae latae muscle. The patient initially opted for traditional Chinese herbal treatment, which we believe, aggravated the growth of the tumor. Radiographic imaging showed clear tumor margins. The histopathological biopsy of the lesion located in the tensor fasciae latae muscle showed a mixture of mononucleated and multinuclear giant cells composed of mesenchyme spindle-shaped cells positive for CD34 and CD88. The patient was treated through surgical resection of the tumor and scheduled for close follow-up. Since GCT-ST is rare, they are often initially misdiagnosed. These tumors have the tendency to increase in size exponentially within a short period of time, which is why clinical presentation and imaging are necessary for a better pre-operative diagnosis. Radical surgical excision or radiotherapy with close follow-up is recommended for all cases due to the high rate of reoccurrence.


Evaluation of rapid commercial enzyme immunoassay for detection of Giardia lamblia in formalin-preserved stool specimens.
Two hundred twenty-three formalin-preserved stool specimens were evaluated by using ProSpecT Giardia Rapid Assay (membrane bound) (Alexon, Inc., Sunnyvale, Calif.). Enzyme immunoassay (EIA) results were compared with those by conventional microscopic examination. Two hundred four specimens were negative by both methods, and 13 (6.3%) were positive. Five specimens were negative by initial microscopic exam and positive by EIA; three of these specimens were found to be positive upon extensive microscopic reexamination. The remaining two specimens were from patients who previously tested positive and who had recurrent symptoms of or responded to therapy for giardia. Therefore, we consider both cases to be true positives. One specimen exhibited a single cyst by microscopic exam and was negative by EIA Resolved results yielded a relative sensitivity of 95%, a relative specificity of 100%, a positive predictive value of 99.6%, and a negative predictive value of 100%, compared with a sensitivity of 74% for conventional microscopy.


A proportional analysis of some facial height and depth variables in 10 to 16 year old children.
A method for analysing the horizontal and vertical proportions of the face is described, based on natural head orientation (NHO). It demonstrates how individual deviations from the mean proportions can be quantified both horizontally and vertically. Correlation between facial depth to height (index 1) and the mandibular plane angle was determined and found to be fairly strong and highly significant (r = 0.5, P < 0.001). Facial depth to height and lower facial height to total facial height (index 2) relationships were found to be strongly correlated at each age between 10 and 16 years, with only small mean differences. For this reason the norm values presented for 12-year-old children for indices 1 and 2 should be applicable to orthodontic patients within this age range. The relationship between mandible and maxilla (index 3) increases continually between 10 and 16 years in boys, and between 10 and 14 years in girls, about 0.3 units a year. It can provide supplementary information for individual case analysis. For boys the increase was 2.2 units per year between 14 and 16 years of age.


Retroverted epiglottis presenting as a variant of globus pharyngeus.
We describe a series of four patients who presented with 'high globus pharyngeus', who all had an abnormally curled epiglottis tip touching and indenting the tongue base. The actual incidence of 'curling epiglottis', as well as the potential impact of this variation in persistent globus symptoms, is not known. We therefore describe for the first time a series of patients with this anatomical variant of the epiglottis, each of whom experienced unresolved globus symptoms despite receiving intensive medical treatment. In the literature, the success rate for improvement in symptoms following medical treatment ranges from 68 to 80 per cent. Following CO2 laser partial epiglottectomy, all four patients experienced complete relief of their symptoms. We advocate consideration of this treatment for high globus pharyngeus that fails to respond to conservative treatment, in cases with proven curled epiglottis on endoscopic examination.


Revival of Ancient Marine Dinoflagellates Using Molecular Biostimulation.
The biological processes involved in the preservation, viability, and revival of long-term dormant dinoflagellate cysts buried in sediments remain unknown. Based on studies of plant seed physiology, we tested whether the revival of ancient cysts preserved in century-old sediments from the Bay of Brest (France) could be stimulated by melatonin and gibberellic acid, two molecules commonly used in seed priming. Dinoflagellates were revived from sediments dated to approximately 150 years ago (156 ± 27, 32 cm depth), extending the known record age of cyst viability previously established as around one century. A culture suspension of sediments mixed with melatonin and gibberellic acid solutions as biostimulants exhibited germination of 11 dinoflagellate taxa that could not be revived under controlled culture conditions. The biostimulants revived some dinoflagellates from century-old sediments, including the potentially toxic species Alexandrium minutum. The biostimulants showed positive effects on germination on even more ancient cysts, showing dose-dependent effects on the germination of Scrippsiella acuminata. Concentrations of 1, 10, and 100 µM melatonin and gibberellic acid promoted germination. In contrast, 1,000 µM solutions, particularly for melatonin, drastically decreased germination, suggesting a potential noxious effect of high doses of these molecules on dinoflagellate revival. Our findings suggest that melatonin and gibberellic acid are involved in the stimulation of germination of dinoflagellate cysts. These biostimulants can be used to germinate long-term stored dinoflagellate cysts, which may promote studies of ancient strains in the resurrection ecology research field.


Generalized pustular psoriasis-like widespread eruption following COVID-19 infection in a patient with spondyloarthropathy on adalimumab.
Generalized pustular psoriasis (GPP) is a form of pustular psoriasis that is distinguished by recurring or persistent outbreaks of non-acral primary sterile pustules. These eruptions can occur with or without systemic inflammation. Various factors, such as medications, stress and viral infection, have been identified as potential triggers for GPP flares. While several cases have detailed GPP-like eruptions in the setting of coronavirus disease 2019 (COVID-19) infection, few have explored the interplay between infection and biologic use in the development of GPP. In this case, we detail the history and management of a 45-year-old male patient with a prior history of spondyloarthropathy managed on a tumour necrosis factor-α inhibitor and recent COVID-19 infection presenting with a new, spreading pustular rash.


Change in role perception, role conflict, and psychological health of working mothers.
A model of the interrelationship among Change in Role Perception, Role Conflict, and Psychological Health of working mothers is introduced. The model posits that Change in Role Perception after the birth of children influences Psychological Health directly or indirectly through Role Conflict. The model was tested with a sample of 192 employed mothers (aged 26-45 years) with at least one child under 11 years of age and who lived in either Melbourne or Canberra, Australia. As expected, scores on Role Conflict predicted all four measures of Psychological Health (Anxiety, Self-esteem, Uptight, and Worn Out). Change in scores on Role Perception predicted Self-esteem and Worn Out. Geographic location predicted scores for Uptight and Worn Out and Occupational Type predicted scores for Worn Out, perhaps due to perceived social support. There are theoretical reasons for maintaining the model's structure. Refinement of methodology, measurement of Change in Role Perception, and possible adoption of a longitudinal approach is recommended. It is concluded that measuring experienced role conflict and change in role perception should be taken into account in any consideration of women's psychological health.


High variability of plasmid uptake rates in Escherichia coli isolated from sewage and river sediments.
The horizontal transfer of plasmids is a key mechanism behind the spread of antibiotic resistance in bacteria. So far, transfer rate constants were measured for a variety of plasmids, donors and recipients. The employed strains typically had a long history in laboratories. Existing data are, therefore, not necessarily representative for real-world environments. Moreover, information on the inter-strain variability of plasmid transfer rates is scarce. Using a high-throughput approach, we studied the uptake of RP4 by various Escherichia coli recipients using Serratia marcescens as the donor. The recipient strains were isolated from human-borne sewage and river sediments. The rate constants of plasmid transfer generally followed a log-normal distribution with considerable variance. The rate constants for good and poor recipients (95 and 5% quantile) differed by more than three orders of magnitude. Specifically, the inter-strain variability of the rate constant was large in comparison to alterations induced by low-level antibiotic exposure. We did not find evidence for diverging efficiencies of plasmid uptake between E. coli recipients of different origin. On average, strains isolated from river bottom sediments were equally efficient in the acquisition of RP4 as isolates extracted from sewage. We conclude that E. coli strains persisting in the aquatic environment and those of direct human origin share a similar intrinsic potential for the conjugative uptake of certain plasmids. In view of the large inter-strain variability, we propose to work towards probabilistic modeling of the environmental spread of antibiotic resistance.


Deciphering the Role of Polyphenols in Sports Performance: From Nutritional Genomics to the Gut Microbiota toward Phytonutritional Epigenomics.
The individual response to nutrients and non-nutrient molecules can be largely affected by three important biological layers. The gut microbiome can alter the bioavailability of nutrients and other substances, the genome can influence molecule kinetics and dynamics, while the epigenome can modulate or amplify the properties of the genome. Today the use of omic techniques and bioinformatics, allow the construction of individual multilayer networks and thus the identification of personalized strategies that have recently been considered in all medical fields, including sports medicine. The composition of each athlete's microbiome influences sports performance both directly by acting on energy metabolism and indirectly through the modulation of nutrient or non-nutrient molecule availability that ultimately affects the individual epigenome and the genome. Among non-nutrient molecules polyphenols can potentiate physical performances through different epigenetic mechanisms. Polyphenols interact with the gut microbiota, undergoing extensive metabolism to produce bioactive molecules, which act on transcription factors involved in mitochondrial biogenesis, antioxidant systems, glucose and lipid homeostasis, and DNA repair. This review focuses on polyphenols effects in sports performance considering the individual microbiota, epigenomic asset, and the genomic characteristics of athletes to understand how their supplementation could potentially help to modulate muscle inflammation and improve recovery.


Tensorizing GAN With High-Order Pooling for Alzheimer's Disease Assessment.
It is of great significance to apply deep learning for the early diagnosis of Alzheimer's disease (AD). In this work, a novel tensorizing GAN with high-order pooling is proposed to assess mild cognitive impairment (MCI) and AD. By tensorizing a three-player cooperative game-based framework, the proposed model can benefit from the structural information of the brain. By incorporating the high-order pooling scheme into the classifier, the proposed model can make full use of the second-order statistics of holistic magnetic resonance imaging (MRI). To the best of our knowledge, the proposed Tensor-train, High-order pooling and Semisupervised learning-based GAN (THS-GAN) is the first work to deal with classification on MR images for AD diagnosis. Extensive experimental results on Alzheimer's disease neuroimaging initiative (ADNI) data set are reported to demonstrate that the proposed THS-GAN achieves superior performance compared with existing methods, and to show that both tensor-train and high-order pooling can enhance classification performance. The visualization of generated samples also shows that the proposed model can generate plausible samples for semisupervised learning purpose.


Three-dimensional finite element simulations of the dynamic response of a fingertip to vibration.
Although excessive dynamic deformation of the soft tissues in the fingertip under vibration loading is thought to induce hand-arm vibration syndrome, the in vivo distributions of the dynamic stress/strain of the tissues in the fingertip under vibration conditions have not been studied because they cannot be measured experimentally. In the present study, we analyzed the dynamic responses of a fingertip to vibrations by extending our previously proposed three-dimensional finite element (FE) model. The FE model of the fingertip contains the essential anatomical structures of a finger, such as skin layers (dermis and epidermis), subcutaneous tissue, bone, and nail. Our analysis indicated that the fingertip has a major local resonance around 100 Hz and that the vibration displacement in the soft tissues under the nail bed is less than 10% of those in the finger pad for all precompression levels and vibration range. The resonant frequency of the fingertip was found to increase from 88 Hz to 125 Hz with the static precompression increasing from 0.5 mm to 2.0 mm. These results suggest that structural and functional changes in vascular function will likely initiate from the fingerpad, the location that undergoes the greatest deformation during vibration exposure. The current predictions are qualitatively consistent with the physiological data collected from workers with vibration white finger.


Occupational safety and health aspects of voice and speech professions.
A well-functioning voice is an essential tool for one third of the labour force. Vocal demands vary to a great extent between the different voice and speech professions. In professions with heavy vocal loading (e.g. school and kindergarten teachers), occupational voice disorders threatening working ability are common. Vocal loading is a combination of prolonged voice use and additional loading factors (e.g. background noise, acoustics, air quality) affecting the fundamental frequency, type and loudness of phonation or the vibratory characteristics of the vocal folds as well as the external frame of the larynx. The prevention and treatment of occupational voice disorders calls for improved occupational safety and health (OSH) arrangements for voice and speech professionals. On the basis of epidemiological and acoustic-physiological research, the presence of risk to vocal health can be substantiated. From the point of view of the physical load on the vocal apparatus, loading-related physiological changes (adaptation) may play a role in the occupational risk. Environmental factors affect vocal loading changes. In teaching professions, the working environment is shared with children, who benefit from amendments of OSH legislation concerning their teachers.


Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.
Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy. Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone. The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all P<0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (P<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups. KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.


Synthesis of DL-alpha-tocopherol-ligated phospholipids.
A three-step synthesis of DL-alpha-tocopheryl-6-O-phosphorylcholine and its -6-O-phosphorylethanolamine homologue is described. The reaction pathway involves the conversion of DL-alpha-tocopherol to the corresponding 2-bromoethyl phosphate, hydrolytic cleavage of the remaining phosphorochloridate bond and treatment of the diester intermediate formed with either aqueous trimethylamine or ammonia to give the aminated target derivatives in good overall yields (61-67%). The compounds represent new models of ligated lipid mediators in which a vitamin E-unit is covalently bonded to a naturally occurring phospholipid fragment.


The Interplay of MicroRNAs in the Inflammatory Mechanisms Following Ischemic Stroke.
Immunity and inflammation are important parameters of the pathophysiology of stroke, a destructive illness that is the second most common cause of death worldwide. Following ischemic stroke, neuroinflammation plays a critical role in neurodegeneration and brain injury. MicroRNAs (miRNAs) are a class of endogenously expressed, noncoding RNA molecules that function to inhibit mRNA translation. Recent studies demonstrate that miRNAs are key regulators of inflammatory processes contributing to ischemic stroke injuries. Several miRNAs, and their target genes, have been shown to play a critical role in the innate inflammatory responses mediated by immune cells. The capacity of miRNAs to regulate several target genes demonstrates their exceptional importance in neuroinflammatory therapeutics following ischemic stroke. In this review, we focus on the miRNAs associated with ischemic neuroinflammation and describe the potential of miRNAs as biomarkers of neuroinflammation and promising therapeutic agents for modulation of deleterious inflammatory responses following ischemic stroke.


Seasonal Changes in Metabolism and Cellular Stress Phenomena in the Gilthead Sea Bream (Sparus aurata).
Seasonal temperature changes may take organisms to the upper and lower limit of their thermal range, with respective variations in their biochemical and metabolic profile. To elucidate these traits, we investigated metabolic and antioxidant patterns in tissues of sea bream Sparus aurata during seasonal acclimatization for 1 yr in the field. Metabolic patterns were assessed by determining lactate dehydrogenase, citrate synthase, and β-hydroxyacyl CoA dehydrogenase activities, their kinetic properties and plasma levels of glucose, lactate, and triglycerides and tissue succinate levels. Oxidative stress was assessed by determining antioxidant enzymes superoxide dismutase, catalase, and glutathione reductase activities and levels of thiobarbituric acid reactive substances. Xanthine oxidase (XO) activity was determined as another source of reactive oxygen species (ROS) production. Furthermore, we studied the antiapoptotic protein indicator Bcl-2 and the apoptotic protein indicators Bax, Bad, ubiquitin, and caspase as well as indexes of autophagy (LC3B II/LC3B I and SQSTM1/p62) in the liver and the heart to identify possible relationships between oxidative stress and cell death. The results indicate clear seasonal metabolic patterns involving oxidative stress during summer as well as winter. During cold acclimatization, lipid oxidation is induced, while during increased temperatures, warm-induced metabolic activation and carbohydrate oxidation are observed. Thus, oxidative stress seems to be more prominent during warming because of the increased aerobic metabolism. The seasonal profile of apoptosis and XO as another source of ROS matches the results obtained in the laboratory and are interpreted within the framework of oxygen- and capacity-limited thermal tolerance.


Crystallinity of mineral deposited in arterial walls in the course of arteriosclerosis in diabetics and in patients with normal carbohydrate metabolism.
A comparison was made of the amount and crystallinity of mineral deposited in the course of the arteriosclerosis in arterial walls in diabetic patients and in individuals with normal carbohydrate metabolism. The macroscopically unchanged tunica intima, fibro-lipidic plaques and bone-like lamellae were taken from aorta thoracalis , aorta abdominalis, arteriae femorales and arteriae coronariae in the course of the autopsy of 17 insulin dependent diabetic individuals and of 9 persons with arteriosclerosis, but with normal carbohydrate metabolism, called control group. The total inorganic constituents in the three kinds of samples were determined by ashing of dried samples at 600 degrees C for 6 h. Crystallinity of mineral was defined as the ratio of the spins connected with the radiation-induced stable paramagnetic centers present in the crystalline lattice of hydroxyapatite crystal, to the total ash content of the sample. An increase in the amount and in the crystallinity of deposited mineral was observed when consecutive stadia of development of arteriosclerotic lesions were compared. This phenomenon resembles the maturation of mineral observed in the course of bone development.


Synchronous colon cancer with pulmonary metastasis and follicular variant of papillary thyroid cancer metastasising to kidney.
Thyroid malignancies are one of the fastest growing cancers in the world, with the majority being papillary thyroid cancer. Follicular variant of papillary thyroid cancer accounts for about 10%-20% of papillary thyroid carcinomas. The usual sites for metastases of these tumours are lungs and bones with renal metastases being extremely rare. We describe a case of a 64-year-old woman who presented with abdominal pain. On subsequent imaging, she was found to have a colonic mass with metastatic lesions in the lungs and tumour involving left kidney. On biopsy and immunohistochemical staining, the renal mass showed positivity for thyroid cancer markers. Thyroid scan was noted to be negative and the patient was placed on active surveillance after undergoing chemotherapy for colonic adenocarcinoma.


Spinal Instability Predictive Scoring System for Subsequent Fracture After Bone Cement Augmentation in Patients with Osteoporotic Vertebral Compression Fracture.
Bone cement augmentation procedures (vertebroplasty and kyphoplasty) are the primary treatments for osteoporotic vertebral compression fracture (VCF). However, these procedures are associated with various problems resulting in subsequent fracture. The purpose of this study was to evaluate the spinal instability factors related to subsequent fracture after vertebral augmentation procedures. We retrospectively reviewed patients who underwent augmentation procedures for osteoporotic VCF. Between May 2011 and November 2014, 285 patients (vertebroplasty, n = 231; kyphoplasty, n = 54) were enrolled. Subsequent fractures were classified into 4 types based on the fracture patterns: 1) no subsequent fracture, 2) neofracture, 3) hammer fracture (new vertebral fractures involving another vertebra without a definitive history of trauma), and 4) kyphotic compression fracture. We analyzed subsequent fracture patterns and their occurrence rates according to factors that may induce subsequent fracture and developed a predictive scoring system with respect to the hammer fracture occurrence rate. We classified all cases into 4 groups (A,B,C,D) according to Spinal Instability Predictive Scoring System score. Groups A, B, C, and D were defined by total scores of 0∼5, 6∼10, 11∼15, and 16∼20, respectively. The subsequent fracture types for vertebroplasty were as follows: no subsequent fracture (n = 112; 48.28%); hammer fracture (n = 65; 28.02%); neofracture (n = 35; 15.09%); and kyphotic compression fracture (n = 19; 8.19%). According to the total scores, the occurrence rate of subsequent hammer fracture (no subsequent fracture, hammer fracture, neofracture, and kyphotic compression fracture) were as follows: group A (84.21%, 0%, 10.52%, and 5.26%), group B (64.58%, 10.45%, 12.5%, and 12.5%), group C (39.39%, 33.3%, 15.15%, and 12.12%), and group D (11.67%, 63.3%, 21.67%, and 3.33%). Predictive scores can be calculated and used to predict the possibility of subsequent fracture according to scores. Group D showed the highest predictive scores and will need more preventative treatment.


[Reflolux--a new test system for the self control of blood glucose for diabetics].
Correctness and accuracy of Reflolux, a new microprocessor-controlled minireflectometer for measuring blood-glucose concentrations, were tested in ten instruments. There was good agreement between the Reflolux values and those obtained in the laboratory with the hexokinase method, over the entire range of 40-350 mg/dl with a relatively small margin of error. Thus the Reflolux provides even in the hypoglycaemic range values accurate enough for everyday use by a diabetic. An important advantage of this test system lies in the use of Haemo-Glukotest 20-800 test strips which, in conjunction with the Reflolux, provide a visual color comparison for blood-glucose levels in the range of 20-800 mg/dl.


Sensor Fault and Delay Tolerant Control for Networked Control Systems Subject to External Disturbances.
In this paper, the problem of sensor fault and delay tolerant control problem for a class of networked control systems under external disturbances is investigated. More precisely, the dynamic characteristics of the external disturbance and sensor fault are described as the output of exogenous systems first. The original sensor fault and delay tolerant control problem is reformulated as an equivalence problem with designed available system output and reformed performance index. The feedforward and feedback sensor fault tolerant controller (FFSFTC) can be obtained by utilizing the solutions of Riccati matrix equation and Stein matrix equation. Based on the designed fault diagnoser, the proposed FFSFTC is further reconstructed to compensate for the sensor fault and delayed measurement effects. Finally, numerical examples are provided to illustrate the effectiveness of our proposed FFSFTC with different cases with various types of sensor faults, measurement delays and external disturbances.


Photochemical mechanisms of radiationless deactivation processes in urocanic acid.
Urocanic acid is a UV filter found in human skin that protects the skin from UV damage but has also been linked to the onset of skin cancer and to photoimmunosuppression. We report on ab initio investigations of two rotameric forms of each of the two tautomers of neutral (E)- and (Z)-urocanic acid. We have computed the vertical singlet excitation energies of eight isomers and have explored the singlet excited-state reaction paths of several photochemical processes for radiationless excited-state deactivation: the E/Z photoisomerization, an electron-driven proton transfer for an intramolecularly hydrogen-bonded Z isomer, as well as the hydrogen-atom detachment process and the ring-puckering process involving the NH group inherent to the imidazole moiety. We have optimized the S1/S0 conical intersections for each of these processes and located additional ππ*/nπ* conical intersections. Because of the reversed energetic order of the nπ* and ππ* states in the N3H and N1H tautomers, an energy window exists where the N3H tautomers can be excited to the nπ* state, from which only the photoisomerization process is accessible, while the N1H tautomers can be excited to the ππ* state, from which several deexcitation processes compete from the onset of the absorption. These results explain the unusual dependence of the quantum yield for E→Z photoisomerization on the excitation wavelength. The present work provides novel insight into the complex photochemistry of this biomolecule and paves the way for future computational studies of the photoinduced excited-state dynamics of urocanic acid.


Effect of conversion from cyclosporine A to mizoribine on transplant arteriosclerosis in rat aortic allograft models.
Recent studies suggested that conversion from cyclosporine A (CsA) to antimetabolic agents protects allograft vasculopathy. However, the mechanism of this beneficial effect by the conversion therapy is not fully understood. In the present study, we investigated the effects of conversion from CsA to antimetabolic agent mizoribine (MZR) on the formation of transplant arteriosclerosis in rat aortic allografts. Conversion from CsA to MZR significantly prevented intimal hyperplasia and perivascular inflammatory cell infiltration at 28 days after aortic transplantation. These findings suggest that conversion therapy from CsA to antimetabolic agents might have therapeutic potential in transplant patients with chronic vascular rejection.


Prolyl isomerases do not catalyze isomerization of non-prolyl peptide bonds.
Prolyl isomerases accelerate the cis <--> trans isomerization of prolyl peptide bonds during protein folding and probably also in folded proteins. We asked whether this catalytic function is in fact restricted to prolyl bonds or whether the isomerizations of 'normal' non-prolyl peptide bonds are catalyzed as well. By using the P39A variant of ribonuclease T1 as a substrate we find that the trans --> cis isomerization of the Tyr38-Ala39 bond in the refolding of this protein is not catalyzed by prolyl isomerases of the cyclophilin, FKBP and parvulin families. These enzymes are neither able to catalyze amide bond isomerizations in the proline-free model peptide Ala-Ala-Tyr-Ala-Ala.


Uncovering periodic patterns of space use in animal tracking data with periodograms, including a new algorithm for the Lomb-Scargle periodogram and improved randomization tests.
Periodicity in activity level (rest/activity cycles) is ubiquitous in nature, but whether and how these periodicities translate into periodic patterns of space use by animals is much less documented. Here we introduce an analytical protocol based on the Lomb-Scargle periodogram (LSP) to facilitate exploration of animal tracking datasets for periodic patterns. The LSP accommodates missing observations and variation in the sampling intervals of the location time series. We describe a new, fast algorithm to compute the LSP. The gain in speed compared to other R implementations of the LSP makes it tractable to analyze long datasets (>10(6) records). We also give a detailed primer on periodicity analysis, focusing on the specificities of movement data. In particular, we warn against the risk of flawed inference when the sampling schedule creates artefactual periodicities and we introduce a new statistical test of periodicity that accommodates temporally autocorrelated background noise. Applying our LSP-based analytical protocol to tracking data from three species revealed that an ungulate exhibited periodicity in its movement speed but not in its locations, that a central place-foraging seabird tracked moon phase, and that the movements of a range-resident canid included a daily patrolling component that was initially masked by the stochasticity of the movements. The new, fast algorithm tailored for movement data analysis and now available in the R-package ctmm makes the LSP a convenient exploratory tool to detect periodic patterns in animal movement data.


Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer.
Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. We sought to elucidate the mechanism of TM by exploring its effects on collagen processing and immune function in the tumor microenvironment (TME). Using an exploratory cohort, we identified markers of collagen processing (LOXL2, PRO-C3, C6M, and C1M) that differed between those with breast cancer versus controls. We measured these collagen biomarkers in TM-treated patients on the phase II study and detected evidence of decreased collagen cross-linking and increased degradation over formation in those without disease compared to those who experienced disease progression. Preclinical studies revealed decreased collagen deposition, lower levels of myeloid-derived suppressor cells, and higher CD4+ T-cell infiltration in TM-treated mice compared with controls. This study reveals novel mechanisms of TM targeting the TME and immune response with potential applications across cancer types.


The activity of Cu/Zn-superoxide dismutase and catalase of gastric mucosa in chronic gastritis, and the effect of alpha-tocopherol.
Activity of Cu/Zn superoxide dismutase (SOD) and catalase (CAT) in gastric mucosa was examined in 12 control subjects and 48 patients with various degree of chronic gastritis. Bioptic specimens of mucosa for enzymologic assays were sampled during gastroscopic examination after overnight fasting. Compared to the control group, a significant increase of SOD activity was observed in samples from superficial gastritis and only insignificant changes in samples from atrophic gastritis, while a remarkable and significant increase in the activity of both SOD and CAT was observed in samples from gastritis after partial gastrectomy. Application of vitamin E significantly reduced activities of SOD and CAT in subjects with chronic gastritis. The authors suppose that the increase in the activities of antioxidant enzymes was caused by an increased formation of superoxide anion radical and hydrogen peroxide, both originating from phagocyting leucocytes in inflamed mucosa. The reduced activity of SOD and CAT after application of vitamin E indicates an inhibition of the formation of active oxygen species in gastric mucosa. Relation of chronic gastritis and elevated concentrations of active oxygen species to gastric carcinogenesis is discussed in the report. (Tab. 2, Fig. 1, Ref. 22.)


Celiac Disease Presenting with Peripheral Neuropathy in Children: A Case Report.
Background: Clinically relevant neurological manifestations in children with celiac disease (CD) are unusual, especially when they are considered as signs of the onset of the disease. In this paper, a case of Guillain-Barrè syndrome (GBS) as the first manifestation of CD in a 23-month-old child is reported. Case presentation: We describe a case of CD onset with peripheral neuropathy in a 23-month-old Bulgarian boy presenting with a sudden refusal to walk and absence of deep tendon reflexes in both lower limbs. Neurological symptoms were preceded by two months of gastrointestinal symptoms such as vomiting, abdominal distention, and clear signs of malnutrition and weight loss. When we evaluated the child six months after the onset of the symptoms, clinical and laboratory findings showed clear signs of peripheral neuropathy associated with malnutrition. Serum deamidated gliadin and tissue transglutaminase antibodies were therefore measured. The anti-gliadin levels were more than sixteen times higher than normal and the IgA anti-transglutaminase levels were four times higher than normal. Anti-endomysium antibodies were positive, and human leukocyte antigens (HLA) II typing confirmed a genetic predisposition to CD (DQ2 positive and DQ8 negative). Given the association between the clinical evidence of the disease and the results of the celiac screening tests, a diagnosis of CD was made without biopsy confirmation of the enteropathy. The child began a restricted gluten-free diet that led to complete recovery of the peripheral neuropathy, walking, reflexes, and overall improvement after three months on the diet. Conclusion: Our case underlines the rare but possible associations between CD and peripheral neuropathy in children as an onset symptom, even in the absence of gastrointestinal manifestations, thus suggesting that CD should always be considered in the differential diagnosis of peripheral neuropathy in children. A good knowledge of the extra-intestinal manifestations of CD is essential for the rapid introduction of a gluten-free diet that could be useful for the resolution of the neurological symptoms.


Construction of polyoxometalates-based coordination polymers through direct incorporation between polyoxometalates and the voids in a 2D network.
A series of polyoxometalates (POMs)-based coordination polymers, namely, {[Cu(2,3-Me2pz)(2,5-Me2pz)0.5]4(SiW12O40)(2,5-Me2pz)}n (2,3-Me2pz = 2,3-dimethylpyrazine; 2,5-Me2pz = 2,5-dimethylpyrazine; 1), {[Cu2(4,4'-bipy)4(H2O)4](SiW12O40)(H2O)18}n (4,4'-bipy = 4,4'-bipyridine; 2), {[Cu(2-Mepz)1.5]3(PMo12O40)(H2O)3.5}n (2-Mepz = 2-methylpyrazine; 3), {[Ag(2,3-Me2pz)1.5]4(SiW12O40}n (4), {[Cu(pz)1.5]4(SiW12O40)(H2O)3}n (pz = pyrazine; 5), {[Cu(2,3-Me2pz)1.5]4(SiW12O40)}n (6), {[Cu(4,4'-bipy)1.75]4(SiW12O40)(H2O)2}n (7), and {[Cu2(4,4'-bipy)4(H2O)4](SiW12O40)(4,4'-bipy)2(H2O)4}n (8), were synthesized through direct incorporation between POMs and the voids of the 2D network. Crystal structural analysis reveals that the relationship between the size of the void of the 2D network and that of POMs is of key importance for successful synthesis of POMs-based open metal-organic frameworks. Guest replacement shows that the pore size of the framework constructed through direct incorporation between POMs and the voids of the 2D network is very sensitive to guest molecules.


Comparative study between biologic porcine dermal meshes: risk factors of postoperative morbidity and recurrence.
Different types of biologic mesh have been introduced as an alternative to synthetic mesh for use in repairing contaminated ventral hernias because of their biocompatible nature. The aim of this study was to compare the clinical outcomes of patients who underwent complex ventral hernia repairs with either non cross-linked or cross-linked porcine dermal meshes. This was retrospective analysis from a prospectively maintained database from January 2010 to May 2013. Patients undergoing open incisional hernia repair with a biologic mesh in the presence of a clean-contaminated, contaminated or dirty wound were reviewed. There were 39 patients who underwent single-staged abdominal wall reconstruction for a contaminated ventral hernia with a biologic mesh. In 15 cases, non cross-linked mesh was used (Strattice, n=8; Protexa, n=1; XenMatrix, n=6); a cross-linked mesh was used in the remaining 24 cases (Permacol n=21; CollaMend n=3). The median follow-up was 11.9 ± 10.6 months. The overall morbidity was 71.8% (n=28), with 15.4% (n=6) for grade I, 23.1% (n=9) for grade II, 23.1% (n=9) for grade III (n=3 grade IIIA, n=6 grade IIIB), 7.7% (n=3) for grade IV and 2.6% (n=1) for grade V. In the cross-linked group, there were six complications directly linked to the biologic mesh, compared with three in the non-cross-linked group. Overall wound morbidity was 41.0% (n=16). There were 13 hernia recurrences (33.3%), and recurrence rate was not significantly different for both groups. Despite the high rate of wound morbidity associated with the single-staged reconstruction of contaminated fields, it can be safely performed with biologic mesh reinforcement. Recurrence rate was not significantly different between cross-linked and non cross-linked porcine meshes.


Oleoyl-lysophosphatidylcholine limits endothelial nitric oxide bioavailability by induction of reactive oxygen species.
Previously we reported modulation of endothelial prostacyclin and interleukin-8 production, cyclooxygenase-2 expression and vasorelaxation by oleoyl- lysophosphatidylcholine (LPC 18:1). In the present study, we examined the impact of this LPC on nitric oxide (NO) bioavailability in vascular endothelial EA.hy926 cells. Basal NO formation in these cells was decreased by LPC 18:1. This was accompanied with a partial disruption of the active endothelial nitric oxide synthase (eNOS)- dimer, leading to eNOS uncoupling and increased formation of reactive oxygen species (ROS). The LPC 18:1-induced ROS formation was attenuated by the superoxide scavenger Tiron, as well as by the pharmacological inhibitors of eNOS, NADPH oxidases, flavin-containing enzymes and superoxide dismutase (SOD). Intracellular ROS-formation was most prominent in mitochondria, less pronounced in cytosol and undetectable in endoplasmic reticulum. Importantly, Tiron completely prevented the LPC 18:1-induced decrease in NO bioavailability in EA.hy926 cells. The importance of the discovered findings for more in vivo like situations was analyzed by organ bath experiments in mouse aortic rings. LPC 18:1 attenuated the acetylcholine-induced, endothelium dependent vasorelaxation and massively decreased NO bioavailability. We conclude that LPC 18:1 induces eNOS uncoupling and unspecific superoxide production. This results in NO scavenging by ROS, a limited endothelial NO bioavailability and impaired vascular function.


In vivo measurement of real-time aortic segmental volume using the conductance catheter.
The goal of this investigation was to determine if the conductance catheter technique for chamber volume measurement could be applied in vivo to determine real-time phasic aortic segmental volume. A four-electrode conductance catheter was used to measure time-varying resistance of the descending thoracic aorta in open-chest, anesthetized dogs. Resistance was converted to segmental volume and the slope correction factor (alpha) and parallel conductance volume (Vp) were determined. The results showed excellent linear correlation between conductance and sonomicrometric segmental volume. The correction factors alpha and Vp were found to be empirically related to average vessel diameter. The relatively high values for the slope correction factor (alpha=4.59+/-0.17 SEM) were found to be primarily related to low-resistivity shunt paths probably originating in the periadventitial aortic wall and to a lesser extent to changes in flow-induced increases in blood resistivity, hematocrit, catheter position, and other adjacent tissue resistivity. The results demonstrate that correction factors empirically derived from measurements of mean aortic diameter could be used to determine absolute real-time phasic segmental volume, cross-sectional area, or diameter. The conductance technique may possess the same potential for determining aortic mechanical properties which has already been demonstrated for determining ventricular mechanical properties.


Brg1 determines urothelial cell fate during ureter development.
Developing and adult ureters express the epigenetic regulator Brg1, but the role of Brg1 in ureter development is not well understood. We conditionally ablated Brg1 in the developing ureter using Hoxb7-Cre and found that Brg1 expression is upstream of p63, Pparγ, and sonic hedgehog (Shh) expression in the ureteral epithelium. In addition, epithelial stratification in the basal cells required Brg1-dependent p63 expression, whereas terminal differentiation of the umbrella cells required Brg1-dependent Pparγ expression. Furthermore, the loss of ureteric Brg1 resulted in failure of Shh expression, which correlated with reduced smooth muscle cell development and hydroureter. Taken together, we conclude that Brg1 expression unifies three aspects of ureter development: maintenance of the basal cell population, guidance for terminal differentiation of urothelial cells, and proper investment of ureteral smooth muscle cells.


[Medulloblastoma presenting as an extra-axial tumor in the cerebellopontine angle].
Differences in the imaging characteristic of adult medulloblastomas have been reported, including involvement of lateral cerebellar hemispheres with an extra-axial appearance. We present a case report of this rare circumstance: a 40 year old man presented with a 3 weeks history of headache, morning vomiting and left hearing difficulties. Magnetic resonance imaging revealed a left cerebellopontine angle (CPA) tumor, like a well circumscribed homogeneously enhancing mass. Through a left suboccipital craniectomy the tumor was totally removed. It presented as a cerebellopontine angle tumor, like a meningioma, and not as an intra-axial tumor. Histological analysis revealed that the tumor was composed of densely packed with highly proliferative cells that produce a dense intercellular reticulin fiber network. Inmunohistochemical analysis showed positive expression to synaptophysin, specific neuronal enolase and cromogranin. Histological diagnosis was crucial to define it as a desmoplastic medulloblastoma the present case and to perform postoperative adjuvant therapy. Neurosurgeons should be aware of the possibility that a CPA tumor is of intraaxial origin, because this increase the variability on pathological diagnosis.


[A case of lynch syndrome treated laparoscopically for multiple colon cancers].
Lynch syndrome is an inherited syndrome associated with the development of colorectal, endometrial, stomach, and other cancers; it is caused by defects in the mismatch repair genes. Such patients are at risk of developing multiple abdominal cancers after colectomy, and the presence of adhesions may render future abdominal surgeries difficult. We recommend that patients with Lynch syndrome should be considered good candidates for laparoscopic surgery. A 43-year-old Japanese man was admitted following a positive fecal occult blood test result. The patient was diagnosed with multiple colon cancers in the right colon. He had undergone endoscopic mucosal resection for a colon polyp when he was 24 years of age. Two people among his father's second-degree relatives had colorectal cancer, and he fulfilled the revised Bethesda guidelines. He underwent laparoscopic-assisted right hemicolectomy and D3 lymph node dissection. Microsatellite instability testing indicated the presence of MSI-H, and genetic testing demonstrated a pathogenic mutation of MLH-1.


Phase II study of paclitaxel and carboplatin for malignant melanoma.
Conventional chemotherapy in the treatment of malignant melanoma has been disappointingly ineffective. Although the most active single agent is dacarbazine, numerous trials support the activity of platinum analogs against melanoma. Several recent trials also demonstrate the single-agent activity of paclitaxel, and support the administration of these agents together in the treatment of a number of solid tumors. We conducted a phase II study treating patients with metastatic melanoma with paclitaxel as a 3-hour infusion of 175 mg/m2, and carboplatin dosed to yield an area under the curve of 7.5 administered during 30 minutes. Patients were previously untreated or treated once with a regimen not including a platinum or taxane agent and had a performance status of 0 or 1. Seventeen patients (8 males; 9 females; average age 51) were enrolled. Thirty-three percent of patients had disease involving the skin, 40% lungs, 33% lymph nodes, 26% liver, and 13% other visceral organs. Anaphylactic reactions developed in two patients associated with paclitaxel infusion, and the patients were subsequently taken off the study. Of the 15 remaining patients, 3 (20%) had partial responses, 7 (47%) had stable disease, and 5 (33%) showed evidence of progressive disease. Eleven patients experienced grade III or IV hematologic toxicity. All treatment-related toxicities were reversible. There were no treatment-related deaths. The combination of paclitaxel and carboplatin has moderate activity against malignant melanoma, with expected reversible hematologic toxicities. Although not prospectively compared with single agents, the combination of paclitaxel and carboplatin may be a treatment option for some patients. Comparisons with other treatment regimens and the search for additional active compounds against melanoma are needed.


Isolated Thrombosis of the Superior Mesenteric Vein.
Most cases of pancreatitis are mild and self-limited. On the other hand, a few patients with pancreatitis may develop vascular complications. Splenic vein thrombosis is the most common vascular complication of acute pancreatitis. Isolated superior mesenteric vein thrombosis is rare and can lead to gut ischemia and necrosis if not timely diagnosed and managed. We report the case of a 40-year-old patient who presented to the hospital with abdominal pain due to acute pancreatitis, leading to superior mesenteric vein thrombosis, which was timely diagnosed and treated with a good outcome.


Complementary and Integrative Health Education in the Medical School Curriculum: An Interest Survey.
Objective: The use of complementary and integrative health (CIH) modalities continues to increase; yet, there is limited instruction in these methods in undergraduate medical-school curricula. The objective of this research was to evaluate interest in developing a CIH curriculum at the Uniformed Services University of the Health Sciences (USUHS), in Bethesda, MD. Materials and Methods: Students and faculty of the USUHS were emailed a 10-question online survey and responded via a Likert scale and open-ended questions. Results: There was interest in learning more about CIH; 65% of student survey respondents and 61% of faculty survey respondents indicated that they "probably" or "definitely" believe that a curriculum in CIH should be instituted at the USUHS. Conclusions: The addition of a curriculum in CIH would be beneficial to future patients who will benefit from the students' additional knowledge and experiences. This curriculum would also benefit the students who would be able to use their knowledge of CIH practices to relieve stress and mitigate burnout.


[Computed tomography in lumbar degenerative disease].
We reported the 18 patients which underwent surgical exploration and reviewed these CT findings. Method. All CT scans were obtained on Somatom II, high resolution CT scanner, with the patient in the supine position. A lateral localizer image (Topogram) was used to select the appropriate intervertebral disk space. The slice thickness was 4 mm. Results. CT findings in lumbar degenerative diseases include bony canal stenosis (central canal stenosis, narrowed lateral recess), soft tissue abnormalities (herniated nucleus pulposus, bulging annulus, hypertrophy and/or ossification of ligamentum flavum, no delineation of nerve root in lateral recess), and spinal instability (spondylolisthesis, vacuum phenomenon). The above three factors contribute to narrowing of spinal canal. No delineation of nerve root or soft tissue replacement of epidural fat in lateral recess suggests that the nerve root may be compressed by some factors. Herniated nucleus pulposus may cause nerve root compression with or without canal stenosis. Conclusion. This study revealed that the CT findings correlated closely with the surgical findings and the site of nerve root compression could be determined.


Altered expression of low affinity insulin-like growth factor binding protein related proteins in hepatoblastoma.
Hepatoblastoma is a poorly understood rare pediatric liver tumour. We have previously shown that the IGF-axis is seriously disrupted in this tumour type. With the recent discovery that several other proteins also have the potential to bind to IGFs called insulin-like growth factor binding protein related proteins (IGFBP-rPs), we undertook an examination of several such genes in a series of hepatoblastomas with matched normal liver tissue. The expression profiles obtained reveal that the expression of these genes are also disturbed in these tumours, and may have implications for our understanding of the IGF-axis and its importance in this disease.


Antiphospholipid antibodies: basic immunology and assays.
Great progress has been made within the past 10 years in characterizing, assaying, and describing mechanism(s) of action in vitro of antiphospholipid antibodies (a-PL Abs); three prominent members are reagin, anticardiolipin antibodies (a-CL Abs), and the lupus anticoagulants (LAC). The major focus of this review is on basic and current biochemical and immunologic research. First, the biochemistry, structural composition, and sources of anionic and dipolar ionic (zwitterionic) phospholipids are discussed together with several serum antibodies directed to these phospholipids. Cardiolipin, the most acidic phospholipid (net negative charge of 2 at pH 7.0) has been historically important as an antigen for testing reagin in syphilis serology, and currently is part of the antigenic composition used in the Venereal Disease Research Laboratory (VDRL) tests. In this connection, the chronic biological false-positive test for syphilis and the LAC are discussed in association with autoimmune disorders such as systemic lupus erythematosus. Second, a naturally occurring plasma anticoagulant in vitro and a critical cofactor for binding of purified autoimmune a-CL Abs to cardiolipin is considered, the beta 2-glycoprotein I (beta 2-gpI). This single-chain plasma polypeptide is highly glycosylated, has 326 amino acids, a molecular weight of 50 kD, and is characterized by repeating amino acid motifs or domains that structurally resemble multiple loops. The highly cationic C-terminal fifth domain binds to anionic phospholipids. The beta 2-gpI is a member of the short consensus repeat superfamily of proteins, and is compared with other proteins with similar domains. Third, experiments are detailed for defining LAC and distinguishing it from other a-CL Abs. Cofactors are also associated with LAC and include beta 2-gpI, prothrombin, protein C, protein S, tissue factor, and factor XI. Thus, LAC antibodies are heterogeneous, and no individual assay can detect all LACs. Because patients with syphilis and other infectious diseases have no cofactor associated with a-CL Abs, their plasma LACs are negative. The a-CL Abs found in infection are not associated with the clinical features of the antiphospholipid syndrome. LAC assays are important because of the pathogenetic association with clinical observations of venous and arterial thrombosis, thrombocytopenia, and recurrent fetal loss. Finally, reports leading to development of currently used direct solid-phase enzyme-linked immunosorbent assays (ELISA) for testing a-PL Abs are outlined; these developments have greatly increased understanding of the basic immunology of target antigens and their respective antibodies. Of significance, a-CL Abs cross-react with other anionic phospholipids. Additionally, the results of these assays led to the realization that high levels of circulating a-PL Abs over long periods are associated with a number of clinical problems now known collectively as the antiphospholipid syndrome.


Synthesis of Fe3O4/graphene/TiO2 composites for the highly selective enrichment of phosphopeptides from biological samples.
In this work, Fe3O4/graphene/TiO2 composites with a large surface area were designed and synthesized for the selective extraction and enrichment of phosphopeptides from biological samples. First, magnetic graphene was prepared according to our previous method. Next, we made the Fe3O4/graphene/TiO2 composite precursor using tetrabutyl titanate. Fe3O4/graphene/TiO2 composites were obtained after solvothermal and calcination treatments. We used standard protein-digestion solutions and human liver samples to test the enrichment ability of the obtained Fe3O4/graphene/TiO2 composites. The experimental results demonstrate that Fe3O4/graphene/TiO2 composites have a good phosphopeptide enrichment ability.


Smart Responsive Azo-Copolymer with Photoliquefaction for Switchable Adhesive Application.
The development and utilization of switchable adhesives are considered to be an essential target to solve the problems of their separation and recycling in some specific service environments, such as the preparation or repair process of electronic devices. Intelligent materials with controllable phase transition are utilized to fabricate switchable adhesives because of the significantly diverse adhesion strengths in different phase states. Photoresponsive azobenzene and its derivatives usually possess different melting temperatures (Tm) or/and glass transition temperatures (Tg) of the cis-trans isomers, which are beneficial to making the photoinduced solid-liquid phase transition for switchable adhesive application possible. Here, a novel three-component azo-copolymer (PNIM-Azo) with fast and reversible photoinduced solid-liquid phase transition has been designed and synthesized. PNIM-Azo possesses reversible bonding/debonding processes, resulting from the different adhesion strengths between trans-configuration PNIM-Azo in the solid state and cis-configuration in the liquid state. Moreover, by incorporating commercialized 2-methoxyethyl acrylate and N-isopropylacrylamide with O and N heteroatoms into the copolymer, the trans-configuration PNIM-Azo possesses the highest adhesion strength (∼11 MPa between two glass substrates) among all of the reported azobenzene-based switchable adhesives, which could be attributed to the increase in the entanglement effect because of the H-bond in the polymer chains formed by introducing heteroatoms. Our synthesized PNIM-Azo copolymer provides an alternative for designing and developing switchable adhesives with high adhesion strength for some electronic production processes.


Evaluation of the effect of trypsin digestion buffers on artificial deamidation.
Nonenzymatic deamidation occurs readily under the condition of trypsin digestion, resulting in the identification of many artificial deamidation sites. To evaluate the effect of trypsin digestion buffers on artificial deamidation, we compared the three commonly used buffers Tris-HCl (pH 8), ammonium bicarbonate (ABC), and triethylammonium bicarbonate (TEAB), and ammonium acetate (pH 6), which was reported to reduce Asn deamidation. iTRAQ quantification on rat kidney tissue digested in these four buffers indicates that artificial Asn deamidation is produced in the order of ammonium acetate < Tris-HCl < ABC < TEAB, and Gln deamidation has no significant differences in all tested buffers. Label-free experiments show the same trend, while protein and unique peptide identification are comparable using these four buffers. To explain the differences of these four buffers in producing artificial Asn deamidation, we determined the half-life of Asn deamidation in these buffers using synthetic peptides containing -Asn-Gly- sequences. It is 51.4 ± 6.0 days in 50 mM of ammonium acetate (pH 6) at 37 °C, which is about 23, 104, and 137 times that in Tris-HCl, ABC, and TEAB buffers, respectively. In conclusion, ammonium acetate (pH 6) is more suitable than other tested buffers for characterizing endogenous deamidation and N-glycosylation.


Insights from the predicted structural analysis of carborane substituted withaferin A with Indoleamine - 2,3-dioxygenase as a potent inhibitor.
Indoleamine-2,3-dioxygenase (IDO) an immunoregulatory enzyme and emerging as a new therapeutic drug target for the treatment of cancer. Carboranes, an icosahedral arrangement of eleven boron atoms plus one carbon atom with unique pharmacological properties such low toxicity, isosterism with phenyl ring and stability to hydrolysis. On the other hand, carboranes are known to increase the interaction of ligand with non-polar region of the protein provides an excellent platform to explore these carboranes towards designing and development of novel, potent and target specific drug candidates with further enhanced binding affinities. Despite of their many potential applications, molecular modeling studies of carborane-substituted ligands with macromolecules have been rarely reported. Previously, we have demonstrated the promising high binding affinity of Withaferin-A (WA) for IDO. In this present study, we investigated the effect of carborane substitutions on WA compound towards developing novel analogs for target specific IDO inhibition with better potency. Interesting docked poses and molecular interactions for the carborane substituted WA ligands were elucidated. Based on our In-silico studies, carborane substituted at various position of WA has shown enhanced binding affinity towards IDO, worth of considering for further studies.


Carotenoid pigments of facultatively anaerobic spirochetes.
Carotenoid pigments were purified from a previously undescribed, red, halophilic spirochete (spirochete RS1), and from Spirochaeta aurantia strain J1. Both spirochetes are facultative anaerobes and produce pigments when growing aerobically. The major pigments of the two spirochetes were identified by means of chromatographic analysis, absorption spectroscopy, hydride reduction, acetylation and silylation experiments, and mass spectrometry. It was concluded that the major pigment from spirochete RS1 was 4-keto-1',2'-dihydro-1'-hydroxytorulene. This conclusion was further supported by infrared spectroscopy and additional analytical data. The evidence showed that the major pigment from S. aurantia was 1',2'-dihydro-1'-hydroxytorulene. Chromatographic and spectrophotometric evidence indicated that this pigment was also present, as a minor carotenoid component, in spirochete RS1. These pigments have been previously detected almost exclusively in gliding bacteria, such as species of Flexibacter, Stigmatella, and Myxococcus. The occurrence of 4-keto-1',2'-dihydro-1'-hydroxytorulene and 1',2'-dihydro-1'-hydroxytorulene in both spirochetes and gliding bacteria may have significance with respect to the evolutionary development of these organisms.


Perovskite-like Metal Formates with Weak Ferromagnetism and as Precursors to Amorphous Materials.
Three isomorphous compounds M(CHOO)3[NH2(CH3)2] (M = Mn(1 x Mn), Co(2 x Co), Ni(3 x Ni)) have been synthesized in solvothermal conditions. Single-crystal X-ray diffraction shows that they are all crystallized in the trigonal space group R c with small differences in the lattice parameters. Bridged by the three-atom single-bridge CHOO-, M ions form a three-dimensional distorted perovskite-like structure with dimethylamine (DMA) cations located in the cages of the network. Based on the magnetic data, these three 3D compounds are weak ferromagnets with the critical temperature Tc = 8.5 K (1 x Mn), 14.9 K (2 x Co), and 35.6 K (3 x Ni), and for 2 x Co and 3 x Ni, spin reorientation might take place at 13.1 and 14.3 K, respectively. At 1.8 K, hysteresis loops can be observed for all three compounds with the coercivity field ca. 90 Oe (1 x Mn), 920 Oe (2 x Co), and 320 Oe (3 x Ni). The canting angles are estimated to be 0.08 degrees, 0.5 degrees, and 0.6 degrees for 1 x Mn, 2 x Co, and 3.Ni, respectively. The magnetic coupling between MnII ions in 1.Mn was estimated based on the model developed by Rushbrook and Wood for a Heisenberg antiferromagnet on a simple cubic lattice and the best fit gives J = -0.23 cm(-1). At the same time, according to molecular field theory of antiferromagnetism, the J values for compounds 1 x Mn, 2 x Co, and 3 x Ni were estimated to be -0.32 cm(-1), -2.3 cm(-1), and -4.85 cm(-1), respectively. The spin cant in these compounds may originate from the noncentrosymmetric character of the three-atom single-bridge CHOO-. Furthermore, amorphous materials 4 x Mn238, 5 x Mn450, 6 x Co320, and 7 x Ni300 were prepared from precursors 1-3 under an argon atmosphere at different temperatures according to the thermogravimetric analyses. As an interesting result, 5 x Mn450 was confirmed to be an amorphous form of Mn3O4 with a considerably large coercivity field HC = 4.1 kOe at 30 K compared to that value (250 Oe) for bulk Mn3O4.


x-ray irradiation analysis based on wavelet transform in tokamak plasma.
Hard x-ray emission from the Runaway electrons is an important issue in tokamaks. Suggesting methods to reduce the Runaway electrons and therefore the emitted hard x-ray is important for tokamak plasma operation. In this manuscript, we have investigated the effects of external fields on hard x-ray intensity and Magneto-Hydro-Dynamic (MHD) activity. In other words, we have presented the effects of positive biased limiter and Resonant Helical Field (RHF) on the MHD fluctuations and hard x-ray emission from the Runaway electrons. MHD activity and hard x-ray intensity were analyzed using Wavelet transform in the presence of external fields and without them. The results show that the MHD activity and therefore the hard x-ray intensity can be controlled by the external electric and magnetic fields.


Effect of Harvey Rat Sarcoma Virus Mutation in Oral Squamous Cell Carcinoma and Its Influence on Different Populations: A Systematic Review.
The information for protein synthesis is given by the genes. These proteins are responsible for controlling functions like cell growth, differentiation, cell maturation, and cell death. In the case of genetic mutations, the protein functions get disturbed leading to a drastic shift in the normal physiological functions of cell growth, differentiation, and proliferation, making the normal cell cancerous. The Harvey rat sarcoma virus (HRAS) gene is an oncogene that belongs to the rat sarcoma virus (RAS) family. HRAS gene provides the instructions for making the HRAS protein that plays an important role in regulating cell division and when the HRAS gene gets mutated it gets involved in initiating cancer. HRAS mutation has been frequently noted in head and neck cancers; however, the mechanism of HRAS mutation involved in the initiation of oral squamous cell carcinoma (OSCC) still remains unexplored. An elaborate systematic literature search was done in PubMed, Scopus, and Web of Science databases. It was found that the Ras-dependent mutations affect the involved upstream and downstream components of the Ras-Raf-MAPK (rat sarcoma virus-rapidly accelerated fibrosarcoma-mitogen-activated protein kinase) pathway deregulating the signal leading to tumorigenesis. The Ras mutation can affect the Ras-Raf-MAPK pathway at different stages. The disease caused is based on the frequency of the HRAS mutation and it can lead to diverse cellular outcomes as it is mainly associated with cell division, differentiation, growth, survival, and the cell cycle. The crosstalk between the signaling pathways is controlled by the signaling molecules resulting in the creation of molecular networks. The balance of these molecular networks is very important to determine the cellular outcome. This systematic review inspects the molecular network of HRAS and its vital role in carcinogenesis. It is aimed at exploring and summarizing the contributions of the HRAS mutation involved in the pathogenesis of OSCC.


Children of school age: the influence of antiepileptic drugs on behavior and intellect.
The role of antiepileptic drugs in behavior and cognitive function in children is well documented in the literature. In general, behavioral problems occur most frequently with phenobarbital and clonazepam, and appear least often with valproate and carbamazepine. Cognitive impairments occur with phenytoin, are less evident with valproate, and minimal with carbamazepine. Monotherapy, as with adults, leads to improvements in both cognitive abilities and behavior.


New Functional Foods with Cactus Components: Sustainable Perspectives and Future Trends.
The growing interest in a healthy lifestyle has contributed to disseminating perspectives on more sustainable natural resource management. This review describes promising aspects of using cacti in the food industry, addressing sustainable, nutritional, and functional aspects of the plant's production. Our study provides an overview of the potential of cacti for the food industry to encourage the sustainable cultivation of underutilized cactus species and their commercial exploitation. The commercial production of cacti has advantages over other agricultural practices by mitigating damage to ecosystems and encouraging migration to sustainable agriculture. The application of cactus ingredients in food development has been broad, whether in producing breads, jellies, gums, dyes, probiotics, and postbiotic and paraprobiotic foods. However, in the field of probiotic foods, future research should focus on technologies applied in processing and researching interactions between probiotics and raw materials to determine the functionality and bioactivity of products.


Gene signatures developed from patient tumor explants grown in nude mice to predict tumor response to 11 cytotoxic drugs.
Patient tumor explants established subcutaneously in serial passage in nude mice were characterized for their sensitivity towards 11 standard cytotoxic anti-cancer agents. The latter include the alkylating agents cyclophosphamide, ifosfamide, mitomycin C, cisplatin and CCNU, the antimetabolites 5-FU and methotrexate; the topoisomerase II inhibitors adriamycin and etoposide, as well as the tubulin binders paclitaxel and vindesine. The mean number of tumors treated with any of the various drugs was 54 (range 31-78). The tumor xenografts' gene expression profiles were determined using the Affymetrix HG-U133 plus 2.0 mRNA expression array representing approximately 38.500 human genes. The hypothesis was that the correlation of drug response to gene expression would identify gene signatures that can predict the drug response of individual tumors to these agents. Predictive gene signatures were found and subsequently verified using the leave-one-out cross-validation (LOOCV) technique. Tumors were considered as responsive if the drugs effected a tumor volume inhibition to less than 11-41% of the volume of vehicle control tumors (T/C%). The median cut-off over all drugs was a T/C of 25%. Using these criteria, on average one third of the test tumors were sensitive (responders) and two thirds were resistant (non-responders). The bio-informatic analysis yielded predictive gene signatures consisting of 42-129 genes (mean for the 11 drugs: 87 genes). On average, the response rate for predicted responders (83%) was 2.45 fold higher than that for all test tumors (random testing, 34%). This increase of response rates, following signature-guided testing, was consistent for all 11 agents. Conversely, 94% of the predicted non-responders (range: 84-100%) proved to be non-responders in nude mouse studies while the proportion of non-responders among all test tumors was approximately 66%. The majority of genes (59%) making up the predictive gene signatures had an unknown function. Known genes were implicated in cell proliferation, apoptosis, DNA repair, cell cycle, metabolism and transcription. The predictive gene signatures presented here for 11 cytotoxic agents have the potential, if employed in the clinic, to substantially increase tumor response rates compared to empirical drug treatment. However they need to be further validated, both preclinically and clinically.


Cloning and sequence analysis of GmII, a Drosophila melanogaster homologue of the cDNA encoding murine Golgi alpha-mannosidase II.
Using the murine cDNA that encodes Golgi alpha-mannosidase II (GlcNAc transferase I-dependent alpha 1,3[alpha 1,6] mannosidase; EC 22.214.171.124) as a probe to screen a cDNA library made from Drosophila melanogaster (Dm) embryos, we have isolated GmII, the Dm sequence homologue. The 3926-bp cDNA has an open reading frame of 3327 bp and predicts a polypeptide of approx. 127 kDa, a mass similar to that of the murine protein. The deduced mouse and Dm amino acid (aa) sequences share extensive similarity across their entire lengths and are both type-II transmembrane (TM) proteins with short cytoplasmic tails, single TM domains and large hydrophilic C-terminal domains. A region of approx. 200 aa, within the C-terminal domain, has considerable similarity to a corresponding region from several other alpha-mannosidases. GmII has been localized to a single site (85D14-18) on the right arm of chromosome 3.


Time-lag properties of corona streamer discharges between impulse sphere and dc needle electrodes under atmospheric air conditions.
In this study of corona streamer discharges from an impulse generator using a dc power supply, the relationship of the discharge time-lag with the dc bias voltage between the sphere-to-needle electrodes under atmospheric conditions is investigated. Devices utilizing corona discharges have been used to purify air or water, destroy bacteria, and to remove undesirable substances, and in order to achieve fast response times and high power efficiencies in such devices, it is important to minimize the time-lag of the corona discharge. Our experimental results show that (a) the discharge path of a negatively biased needle electrode will be straighter than that of a positively biased needle and (b) the discharge threshold voltage in both the positive and the negative needle electrodes is nearly equal to 33 kV. By expressing the discharge voltage as a power function of time-lag, the extent of corona generation can be quantitatively specified using the exponent of this power function. The observed behavior of a corona streamer discharge between the negative spherical and the positive needle electrodes indicates that the largest power exponent is associated with the shortest time-lag, owing to the reduction in the statistical time-lag in the absence of a formative time-lag.


Comparison of pediatric and adult cerebral arteriovenous malformations.
The authors report 19 consecutive children with cerebral arteriovenous malformations over the period 1978-1992. These patients are compared with a series of 120 consecutive adult patients with the same pathology, managed during the same period. The main clinical and angiographic features, as well as the treatment modalities and outcome are reviewed and compared. Children seem to harbour smaller and simpler lesions than adults. Furthermore, despite a more severe clinical presentation, children appears to fare better than adults. The possibility of evolution of brain arteriovenous malformations is discussed.


Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells.
Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Furthermore, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.


HIV-1 polymorphism: a challenge for vaccine development - a review.
The perspective for the development of anti-HIV/AIDS vaccines became a target sought by several research groups and pharmaceutical companies. However, the complex virus biology in addition to a striking genetic variability and the limited understanding of the immunological correlates of protection have made this an enormous scientific challenge not overcome so far. In this review we presented an updating of HIV-1 subtypes and recombinant viruses circulating in South American countries, focusing mainly on Brazil, as one of the challenges for HIV vaccine development. Moreover, we discussed the importance of stimulating developing countries to participate in the process of vaccine evaluation, not only testing vaccines according to already defined protocols, but also working together with them, in order to take into consideration their local information on virus diversity and host genetic background relevant for the vaccine development and testing, as well as including local virus based reagents to evaluate the immunogenicity of the candidate vaccines.


Screening, diagnosis and treatment of iron deficiency in chronic heart failure: putting the 2016 European Society of Cardiology heart failure guidelines into clinical practice.
Iron deficiency is common in patients with chronic heart failure (CHF) and is associated with reduced exercise performance, impaired health-related quality of life and an increased risk of mortality, irrespective of whether or not anaemia is present. Iron deficiency is a serious but treatable condition. Several randomized controlled clinical trials have demonstrated the ability of intravenous (IV) iron, primarily IV ferric carboxymaltose (FCM), to correct iron deficiency in patients with heart failure with reduced ejection fraction (HFrEF), resulting in improvements in exercise performance, CHF symptoms and health-related quality of life. The importance of addressing the issue of iron deficiency in patients with CHF is reflected in the 2016 European Society of Cardiology (ESC) heart failure guidelines, which recognize iron deficiency as an important co-morbidity, independent of anaemia. These guidelines recommend that all newly diagnosed heart failure patients are routinely tested for iron deficiency and that IV FCM should be considered as a treatment option in symptomatic patients with HFrEF and iron deficiency (serum ferritin < 100 µg/L, or ferritin 100-299 µg/L and transferrin saturation < 20%). Despite these specific recommendations, there is still a lack of practical, easy-to-follow advice on how to diagnose and treat iron deficiency in clinical practice. This article is intended to complement the current 2016 ESC heart failure guidelines by providing practical guidance to all health care professionals relating to the procedures for screening, diagnosis and treatment of iron deficiency in patients with CHF.


New technologies in using recombinant attenuated Salmonella vaccine vectors.
Recombinant attenuated Salmonella vaccines (RASVs) have been constructed to deliver antigens from other pathogens to induce immunity to those pathogens in vaccinated hosts. The attenuation means should ensure that the vaccine survives following vaccination to colonize lymphoid tissues without causing disease symptoms. This necessitates that attenuation and synthesis of recombinant gene encoded protective antigens do not diminish the ability of orally administered vaccines to survive stresses encountered in the gastrointestinal tract. We have eliminated these problems by using RASVs with regulated delayed expression of attenuation and regulated delayed synthesis of recombinant antigens. These changes result in RASVs that colonize effector lymphoid tissues efficiently to serve as "factories" to synthesize protective antigens that induce higher protective immune responses than achieved when using previously constructed RASVs. We have devised a biological containment system with regulated delayed lysis to preclude RASV persistence in vivo and survival if excreted. Attributes were added to reduce the mild diarrhea sometimes experienced with oral live RASVs and to ensure complete safety in newborns. These collective technologies have been used to develop a novel, low-cost, RASV-synthesizing, multiple-protective Streptococcus pneumoniae antigens that will be safe for newborns/infants and will induce protective immunity to diverse S. pneumoniae serotypes after oral immunization.


Riboflavin requirements of Filipino children and non-pregnant, pregnant and lactating women: Studied by the erthrocyte glutathione reductase activation test.
Riboflavin requirements were studied in six non-pregnant, 12 pregnant, 11 lactating women, 20 children aged 4-6 years and 14 children aged 10-12 years. All subjects initially were riboflavin-deficient with erythrocyte glutathione reductase activation coefficient (EGR-AC) of >=1.3, confined in a metabolic ward and repleted with increasing doses of riboflavin during four 10 or 8 day feeding periods. The repletion diet simulated the usual basal diet of the subjects but were modified to contain adequate energy and protein in the pregnant group. Minimum riboflavin requirements determined by regression analysis as intakes required to obtain an EGR-AC value of < 1.3 were: 0.72 ± 0.09 (non-pregnant); 1.36 ± 0.37 (pregnant); 1.31 ± 0.16 (lactating); 0.58 ± 0.10 (children 4-6 years), and 0.70 ± 0.18 mg/d (children 10-12 years). Riboflavin requirements in mg/d, mg/1000 kcal, mg/g protein or mg/kg metabolic body size for the groups varied. Because of the large variability, the use of a single value relating riboflavin requirement to either energy,protein requirements or metabolic body size to calculate requirements for different age groups or gender is deemed inappropriate. It is recommended that riboflavin requirements be expressed in mg/d as determined experimentally for different population groups. Estimated recommended dietary allowances for the groups studied, obtained by adding 30% to the mean minimum riboflavin requirement, are presented.


Diverse application of MRI for mouse phenotyping.
Small animal models, particularly mouse models, of human diseases are becoming an indispensable tool for biomedical research. Studies in animal models have provided important insights into the etiology of diseases and accelerated the development of therapeutic strategies. Detailed phenotypic characterization is essential, both for the development of such animal models and mechanistic studies into disease pathogenesis and testing the efficacy of experimental therapeutics. MRI is a versatile and noninvasive imaging modality with excellent penetration depth, tissue coverage, and soft tissue contrast. MRI, being a multi-modal imaging modality, together with proven imaging protocols and availability of good contrast agents, is ideally suited for phenotyping mutant mouse models. Here we describe the applications of MRI for phenotyping structural birth defects involving the brain, heart, and kidney in mice. The versatility of MRI and its ease of use are well suited to meet the rapidly increasing demands for mouse phenotyping in the coming age of functional genomics. Birth Defects Research 109:758-770, 2017. © 2017 Wiley Periodicals, Inc.


Examining the Phenomenon of the Administrative Burden in Health Care, Allied Health, and Respiratory Care.
Documentation expectations for allied health professional appears to have changed dramatically in the past decade. The purpose of this essay is to discuss the literature related to clinician perceptions of these documentation expectations and changes in the workload attributable to such administrative duties, review the results of a recent pilot project surveying respiratory therapists' perception of documentation, and reflect upon the potential ramifications of excessive documentation. This commentary also discusses some recommendations for the future in terms of the design of documentation systems and the need for additional research to further explore this area.


Collision Tumor of Urothelial Cell Carcinoma and Clear Cell Renal Cell Carcinoma: A Case Report and Review of the Contemporary Literature.
We present a case of synchronous renal cell carcinoma and urothelial carcinoma. Our case was a true collision tumor and both components were high grade. Metastasis to the adrenal gland by the urothelial carcinoma was observed. The morphologic impression was confirmed with GATA3 expression by the urothelial carcinoma component and PAX8 expression by the renal cell carcinoma component. We have reviewed the contemporary literature of this unusual dual diagnosis.


Conceptual design of the gamma-to-electron magnetic spectrometer for the National Ignition Facility.
The Gamma-to-Electron Magnetic Spectrometer (GEMS) diagnostic is designed to measure the prompt γ-ray energy spectrum during high yield deuterium-tritium (DT) implosions at the National Ignition Facility (NIF). The prompt γ-ray spectrum will provide "burn-averaged" observables, including total DT fusion yield, total areal density (ρR), ablator ρR, and fuel ρR. These burn-averaged observables are unique because they are essentially averaged over 4π, providing a global reference for the line-of-sight-specific measurements typical of x-ray and neutron diagnostics. The GEMS conceptual design meets the physics-based requirements: ΔE/E = 3%-5% can be achieved in the range of 2-25 MeV γ-ray energy. Minimum DT neutron yields required for 15% measurement uncertainty at low-resolution mode are: 5 × 10(14) DT-n for ablator ρR (at 0.2 g/cm(2)); 2 × 10(15) DT-n for total DT yield (at 4.2 × 10(-5) γ/n); and 1 × 10(16) DT-n for fuel ρR (at 1 g/cm(2)).


Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy.
Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT), while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control. Patients with National Comprehensive Cancer Network (NCCN) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S-) IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3-5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC) Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was -0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52). Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05). At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9-86). Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical control. The high rate of PSA failure and contralateral local failures in US-IMRT patients, despite careful selection of MRI-screened low-risk patients, serve as a cautionary tale for focal PCa treatments.


Severe Complications from an Unexpectedly High Serum Mycophenolic Acid Concentration in a Patient with Renal Failure Secondary to Lupus Nephritis: A Case Report.
Mycophenolate mofetil (MMF) is used widely to treat lupus nephritis and is considered safer than other immunosuppressive drugs. Reports on severe complications related to MMF are sparse. We report a case of a patient with lupus nephritis in whom severe complications were possibly caused by MMF. The patient was a 17-year-old girl who received a diagnosis of lupus nephritis at the age of 14 years and had been taking steroid and immunosuppressive agents since then. One week after starting MMF 1 g/day instead of mizoribine owing to symptom relapse and serologic data deterioration, she presented with seizure, accompanied by leukopenia, thrombocytopenia, and renal failure. We discontinued MMF because she had extremely high serum mycophenolate acid concentration (88 µg/mL). A few weeks later, she recovered without any complications and was discharged. Although rare, clinicians should be aware that serum mycophenolate acid concentration may become extremely high in the setting of acute kidney injury. In such circumstances, they should perform serum concentration monitoring to avoid possible adverse events.


[COMPARISON OF QuantiFERON® TB GOLD TEST RESULTS BEFORE AND AFTER ENDOTOXIN CONTAMINATION].
In response to a case of endotoxin contamination of tubes used in QuantiFERON® TB Gold (QFT-3G) testing in Japan in 2013, the effect of this contamination on QFT-3G test results was investigated. We analyzed QFT-3G results from 4,258 participants in a tuberculosis contact investigation in Yamagata, Japan from September 2010 to April 2015. Of these, 2,488 samples were collected before the endotoxin contamination, while 1,770 samples were collected after the contamination. Negative control values in the group tested after the contamination were significantly lower than those in the group tested before the contamination (P < 0.0005). The proportion of positive controls that exceeded the calculated limit (10IU/ml) in the group tested after the contamination (87.8%) was lower than that in the group tested before the contamination (96.8%; P < 0.0005). The proportion of intermediate results in the group tested after the contamination (3.2%) was markedly lower than that in the group tested before the contamination (6.6%). Differences in QFT-3G test results were found to be related to a difference in blood collection before or after endotoxin contamination of blood collection tubes. Values resulting from QFT-3G testing were lower in blood samples that were collected after the contamination relative to those collected before the contamination.


L-type amino acid transporter 1 expression in esophageal carcinogenesis according to WHO and Japanese classifications of intraepithelial neoplasia.
L-type amino acid transporter 1 (LAT1) has an essential role in cell proliferation especially in neoplasms. Although immunohistochemical expression of LAT1 has been investigated in invasive esophageal carcinoma, its expression in intraepithelial neoplasia (IEN) has not been reported. Further, classification of esophageal IEN is currently different between the World Health Organization (WHO) and Japanese criteria. Therefore, in this study, immunohistochemical expressions of LAT1 along with Ki-67 were analyzed in 66 esophageal samples of endoscopic submucosal dissection. Extension of cells positive for either marker within the epithelium, along with LAT1 intensity at the base of the epithelium, was evaluated. The results among early IENs, progressed IENs, and invasive carcinoma based on both WHO and Japanese criteria were compared. It was demonstrated that Ki-67+ cells extended toward the superficial layer in IENs, which was more pronounced in progressed compared with early IENs based on both WHO and Japanese criteria. Although similar results were obtained for LAT1+ cells, LAT1+ cell extended more in invasive carcinoma than in progressed IENs according to the WHO criteria. Further, LAT1 intensity was different between early and progressed IENs based on the Japanese criteria alone. Thus, use of LAT1 immunohistochemistry and Japanese classification may be more meaningful to characterize esophageal carcinogenesis.